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Migrasome formation is mediated by assembly of micron-scale tetraspanin macrodomains

Nature cell biology, 2019-08, Vol.21 (8), p.991-1002 [Peer Reviewed Journal]

COPYRIGHT 2019 Nature Publishing Group ;Copyright Nature Publishing Group Aug 2019 ;ISSN: 1465-7392 ;EISSN: 1476-4679 ;DOI: 10.1038/s41556-019-0367-5 ;PMID: 31371828

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  • Title:
    Migrasome formation is mediated by assembly of micron-scale tetraspanin macrodomains
  • Author: Huang, Yuwei ; Zucker, Ben ; Zhang, Shaojin ; Elias, Sharon ; Zhu, Yun ; Chen, Hui ; Ding, Tianlun ; Li, Ying ; Sun, Yujie ; Lou, Jizhong ; Kozlov, Michael M ; Yu, Li
  • Subjects: Assembly ; Cell organelles ; Cell research ; Cellular structure ; Cholesterol ; Fibers ; Formation ; Membrane proteins ; Organelles ; Physiological aspects ; Stiffening ; Stiffness
  • Is Part Of: Nature cell biology, 2019-08, Vol.21 (8), p.991-1002
  • Description: Migrasomes are recently discovered cellular organelles that form as large vesicle-like structures on retraction fibres of migrating cells. While the process of migrasome formation has been described before, the molecular mechanism underlying migrasome biogenesis remains unclear. Here, we propose that the mechanism of migrasome formation consists of the assembly of tetraspanin- and cholesterol-enriched membrane microdomains into micron-scale macrodomains, which swell into migrasomes. The major finding underlying the mechanism is that tetraspanins and cholesterol are necessary and sufficient for migrasome formation. We demonstrate the necessity of tetraspanins and cholesterol via live-cell experiments, and their sufficiency by generating migrasome-like structures in reconstituted membrane systems. We substantiate the mechanism by a theoretical model proposing that the key factor driving migrasome formation is the elevated membrane stiffness of the tetraspanin- and cholesterol-enriched macrodomains. Finally, the theoretical model was quantitatively validated by experimental demonstration of the membrane-stiffening effect of tetraspanin 4 and cholesterol.
  • Publisher: England: Nature Publishing Group
  • Language: English
  • Identifier: ISSN: 1465-7392
    EISSN: 1476-4679
    DOI: 10.1038/s41556-019-0367-5
    PMID: 31371828
  • Source: ProQuest Central
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